Stimuli-responsive molecularly imprinted polymers for drug delivery: a review.
ABSTRACT Molecular imprinting is an efficient technique for introducing regions with a highly specific molecular arrangement into a polymeric matrix. The first example of a molecularly imprinted polymer (MIP) was reported half a century ago; however, the use of molecular imprinting has become a well established practical tool only in the last decade. Recently, MIPs are widely used, for example, in chromatographic applications or enzyme antibody mimics. MIPs have also been used in biological applications such as drug delivery systems (DDS), and they have also been successfully applied as excipients in controlled delivery systems. Their huge potential could bring about intelligent drug release; this refers to the release, in a predictable way, of therapeutic agents in response to specific environmental stimuli (the presence of another molecule, pH changes, temperature, etc.). This review is focused on particular intelligent devices of this type that exhibit selective recognition (traps for toxic molecules) and release (of drugs in order to prolong the duration of pharmacological action) in response to specific stimuli. The "stimuli-responsive molecularly imprinted polymers" reviewed in this paper are expected to contribute significantly to the exploration and development of new generations of intelligent and self-regulated drug delivery systems.
Article: Enzyme-responsive intracellular controlled release using nanometric silica mesoporous supports capped with "saccharides".[show abstract] [hide abstract]
ABSTRACT: The synthesis of new capped silica mesoporous nanoparticles for on-command delivery applications is described. The gate-like functional hybrid systems consisted of nanoscopic MCM-41-based materials functionalized on the pore outlets with different "saccharide" derivatives and a dye contained in the mesopores. A series of hydrolyzed starch products as saccharides were selected. The mesoporous silica nanoparticles S1, S2, and S3 containing the grafted starch derivatives Glucidex 47, Gludicex 39, and Glucidex 29 were synthesized. Additionally, for comparative purposes solid S4 containing lactose was prepared. Delivery studies in pure water in the presence of pancreatin or β-d-galactosidase were carried out for S1-S3 and S4, respectively. S1, S2, and especially S3 showed very low release in the absence of enzyme, but displayed cargo delivery in the presence of the corresponding enzyme. Moreover, nanoparticles of S1 were used to study the controlled release of the dye in intracellular media. Cell viability assays using HeLa and LLC-PK1 cells indicated that S1 nanoparticles were devoid of unspecific cell toxicity. The endocytosis process for S1 nanoparticle internalization in HeLa cells was confirmed, and the anchored starch was degraded by the lysosomal enzymes. Furthermore, a new mesoporous silica nanoparticle functionalized with Glucidex 47 and loaded with a cytotoxic, S1-DOX, was developed. The cell viability with S1-DOX decreased due to the internalization of the nanoparticle, enzyme-dependent opening of the saccharide molecular gate and the consequent release of the cytotoxic agent. As far as the authors know, this is the first example of enzyme-induced in-cell delivery using capped silica mesoporous nanoparticles.ACS Nano 10/2010; 4(11):6353-68. · 10.77 Impact Factor
Article: Development of a pH-responsive imprinted polymer for diclofenac and study of its binding properties in organic and aqueous media.[show abstract] [hide abstract]
ABSTRACT: Three different molecularly imprinted polymers (MIPs) for drug delivery of diclofenac in gastrointestinal tract were synthesized employing bulk polymerization method and their binding and release properties were studied in different pH values. Methacrylic acid (MAA), methacrylamide (MAAM) and 4-vinyl pyridine (4VP) were tested as functional monomers and ethylene glycole dimethacrylate (EDMA) was used as a cross-linker monomer in polymeric feed. Binding properties and imprinting factor (IF) of MIPs were studied in comparison with their non-imprinted ones (Blank) in organic and aqueous media. Diclofenac release in aqueous solvents at pH values of 1.5, 6.0 and 8.0, simulating gastrointestinal fluids, were also studied. The results indicated the specific binding of diclofenac to imprinted polymers. Duo to the stronger non-specific bounds in aqueous solutions, IF values decreased in water compared to acetonitrile as an organic medium. Our results proved that all polymers represented pH-responsive diclofenac delivery at above conditions. The data showed that imprinted polymer, prepared by MAA had superior properties, in comparison with other polymers, for minimum release (14%) of drug in gastric acid and maximum release (90%) in basic condition. The results indicated that diclofenac imprinted polymer could be used as a pH-responsive matrix in preparation of a new drug delivery system for diclofenac.Drug Development and Industrial Pharmacy 10/2011; 38(5):616-22. · 1.49 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented.International Journal of Molecular Sciences 01/2011; 12(9):5908-45. · 2.60 Impact Factor